Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine

Ying Wang; Di Gao; Yan Liu; Xiaoqing Guo; Shuojia Chen; Li Zeng; Jinxuan Ma; Xingcai Zhang; Zhongmin Tian; Zhe Yang

doi:10.1016/j.bioactmat.2020.11.016

Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine

Bioact Mater. 2020 Nov 19;6(6):1513-1527. doi: 10.1016/j.bioactmat.2020.11.016. eCollection 2021 Jun.

Authors

Ying Wang¹, Di Gao¹, Yan Liu², Xiaoqing Guo¹, Shuojia Chen¹, Li Zeng¹, Jinxuan Ma¹, Xingcai Zhang^{2

3}, Zhongmin Tian¹, Zhe Yang¹

Affiliations

¹ The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
² John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, United States.
³ School of Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, United States.

Abstract

Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape. However, their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues. Herein, a new poly (acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl) oxyethyl disulfide) (PAAVB) polymer-based intelligent platform with controllable upper critical solution temperature (UCST) was used for the simultaneous delivery of paclitaxel (PTX) and curcumin (CUR). Additionally, a hyaluronic acid (HA) layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells. The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells. Then, the acidic microenvironment and high level of glutathione (GSH) in cancer cells could spontaneously decrease the UCST of polymer, leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli. Significantly, the released PTX and CUR could induce the immunogenic cell death (ICD) to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme respectively. Therefore, the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis.

Keywords: Cancer chemoimmunotherapy; Controllable upper critical solution temperature (UCST); Drug delivery; Immunogenic cell death (ICD); Indoleamine 2,3-dioxygenase 1 (IDO1).